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Pharmacopsychiatry 2013; 46(02): 63-68
DOI: 10.1055/s-0032-1323671
Original paper
© Georg Thieme Verlag KG Stuttgart · New York

Non-Fatal and Fatal Liver Failure Associated with Valproic Acid

M. M. Schmid   *
1   Department of Psychiatry and Psychotherapy III, University of Ulm, Ulm, Germany
,
R. W. Freudenmann   *
1   Department of Psychiatry and Psychotherapy III, University of Ulm, Ulm, Germany
,
F. Keller
2   Department of Child and Adolescent Psychiatry/ Psychotherapy, University of Ulm, Ulm, Germany
,
B. J. Connemann
1   Department of Psychiatry and Psychotherapy III, University of Ulm, Ulm, Germany
,
C. Hiemke
3   Department of Psychiatry and Psychotherapy, University of Mainz, Mainz, Germany
,
M. Gahr
1   Department of Psychiatry and Psychotherapy III, University of Ulm, Ulm, Germany
,
W. Kratzer
4   Department of Internal Medicine I, University of Ulm, Ulm Germany
,
M. Fuchs
5   Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University Medical School, Richmond, USA
,
C. Schönfeldt-Lecuona   *
1   Department of Psychiatry and Psychotherapy III, University of Ulm, Ulm, Germany
› Author Affiliations
Further Information

Publication History

received 10 May 2012
revised 18 July 2012

accepted 19 July 2012

Publication Date:
22 August 2012 (online)

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Abstract

Introduction:

Little is known about hepatotoxicity associated with valproic acid (VPA), a widely used substance in neuropsychiatry.

Methods:

All reported cases to the German Federal Institute for Drugs and Medical Devices between 1993 and 2009 of VPA-induced serious hepatic side effects were evaluated.

Results:

A total of 132 cases of serious VPA-associated liver failure were identified. Approximately one third (34.8%) occurred under VPA monotherapy, while the majority was seen with VPA plus co-medication, most frequently antiepileptics (34.8%) and benzodiazepines (16.7%). A subgroup of 34 cases (25.8%) had a fatal outcome, the largest number reported to date. Of these, 32.4% were under VPA monotherapy and 67.6% under VPA plus concomitant medication. Within the study period a significant increase in the total number of reported cases and the subgroup of fatal cases was found.

Discussion:

This first pharmacovigilance study of VPA-associated liver failure indicates a higher rate of non-fatal and fatal liver failure when VPA is given with co-medication as compared to monotherapy. However, co-medication per se does not increase the risk of fatalities.

Key words

valproic acid - hepatotoxicity - liver failure - pharmacovigilance

* These 3 authors contributed equally to this article.